Developmental Disorders - Lecture 19

Question 1

Malformations

Answer 1

Primary errors of morphogenesis, are usually multifactorial, involving a number of etiological agents including genetic and enviromental factors

Question 2

Disruptions

Answer 2

Distrurbances in otherwise normal morphogenetic processes, example: amnionic band

Question 3

Deformations

Answer 3

Disturbances in otherwise normal morphogenic processes caused by abnormal biomechanical forces like uterine constraints. Clubfoot is an example

Question 4

Sequences

Answer 4

A series of events triggered by one initiation factor.

Example: oligohydroamnios - decresed amniotic fluid - which leads to a variety of events like fetal compression and problems that stem from that

Question 5

Syndromes

Answer 5

Syndromes are constellations of congenital anomalies that are thought to be pathologically related but cannot be explained on the basis of a single local intial event

Ie viral infection

Question 6

Critical period

Answer 6

A window of time in develop where the developing organism is susceptible to insult or development problems

Question 7

Causes of congenital anomalies

Answer 7

Unknown - 50%
Multifactorial - 25%
Environmental - 7%
Genetic - chromosomal 10%, monogenic 8%

Question 8

Gene mutation

Answer 8

Include inborn errors of metabolism - rare

Most commonly autosomal recessive or x-linked

Often effect enzymes and biochemical pathways

Examples: phenylketonuria
Galactosemia
Cystic fibrosis

Question 9

Chromosomal genetic factors

Answer 9

Rearrangements - deletions, duplicatiions, inversiions, translocations

Aneuploidy

• changes in chromosome number (not 2N)
• trisomy 21, trisomy 13, turner syndrome, poly-X syndrome

Question 10

Euplody

Answer 10

Addtion of a complete set of chromosomes
Retention of polar body or fertilization by moroe than one sperm
Early spontaneous abortion

Question 11

What are some infectious agents that can cause birth abnormalities?

Answer 11

Viral infections - rubella, CMV, HSV, Varicella-zoster, flu, mumps, bacterial and protzoans

radiation

Maternal diabeties

Thalidomide

Alcohol

Retinoic acid

Folic Acid

Question 12

What are the effects of thalidomide, alcohol, retinoic acids and folic acid on birth abnormalities?

Answer 12

Retinoic acid - defects mostly related to the neural crest, so facial structures, outflow track of the heart and the thymus.

thalidomine - extreme limb malformation, cardiovascular malformation, no ears, urinary system, GI and facial defects

alcohol - fetal alcohol syndrome

folic acid - anencephaly, growth retardation, cleft lip and palate, hydrocephaly, hypoplastic mandible and low-set ears.

Question 13

What are the effects of radiation or maternal diabetes on birth abnormalilties?

Answer 13

Radiation - predominately CNS defects from spina bifida to mental retardation but also cleft palate, microcephaly, malformation of the viscera, limbs and skeleton

Diabetes - high birth weight and stillborns

Question 14

Dysplasia

Answer 14

An abnormality caused by mechanical forces

-amnionic band constriction

Question 15

Association

Answer 15

A group of anomalies seen in more than one individual that cannot yet be attributed to a definitive cause

Question 16

What is teratology? What is a teratogen?

Answer 16

Teratology literally means “study of monsters”, clinically its the study of congenital malformations

A teratogen is an enviromental agent that causes birth defects

Question 17

Gene mutations associated with birth abnormalities

Answer 17

include inborn errors of metabolism

• mostly autosomal recessive or x-linked
• affect enzymes and biochemical pathways

examples:
- phenylketonuria: accumulation of phenylalanine
- galactosemia: tissue accumulation of galactose 1-phosphate

-cystic fibrosis: CFTR chlorine transporter mutation

Question 18

what are chromosome rearrangements? and examples

Answer 18

deletions, duplications, inversions, translocations

ex - cri du chat syndrome - mentally retarded and microcephaly

Question 19

aneuploidy

Answer 19

changes in chromosome number beyond the 2N state
includes: 
trisomy 21
trisomy 13
turner syndrome
poly-X syndrome

Question 20

Turner Syndrome

Answer 20

X0 - only one X chromosome, 45 total

characteristics:
female with underdeveloped sex characteristics, low hairline, broad chest, folds on neck, usually sterile and usually of normal intelligence

Question 21

Poly-X Syndrome

Answer 21

XXX

usually tall and thin, often fertile and most have normal intelligence

Question 22

what are example of infectious agents that cause birth abnormalities?

Answer 22

Rubella virus 
cytomegalovirus 
treponema 
toxoplasmosis 
zika virus 
herpes simplex
varicella-zoster
flu
mumps

Question 23

Causes and symptoms of neonatal respiratory distress syndrome

Answer 23

immaturity of the lungs, in premature birth, lack of pulmonary surfactant. Pulmonary surfactant makes inspiring easier

Question 24

Causes and symptoms of hydrops

Answer 24

accumulation of edema fluid in the fetus. common cause is blood group incompatibility between mother and fetus - immune hydrops
mother Rh-, baby Rh+

Nonimmune hydrops - causes: cardiovascular defects such as congenital cardiac defects and arrhythmias, chromosomal anomalies and kernicturus

Question 25

Causes and symptoms of eclampsia

Answer 25

high blood pressure in pregnant women
proteinuria - protein in the urine
weight gain
edema

eclampsia - extremely high BP, can cause grand mal seizures or coma

Question 26

kernicturus

Answer 26

brain damage from severe jaundice

Question 27

prematurity

Answer 27

tied with fetal growth restrictions are the second most common cause of neonatal mortality

major risk factors:
preterm premature rupture of placental membranes
intrauterine infections
uterine, cervical and placental structural abnormalities
multiple gestation

Question 28

fetal growth restrictions

Answer 28

fetal factors

• chromosomal disorders
• congenital anomalies
• congenital infections

Placental factos

• umbillical placental vascular anomalies
• placenta previa
• placental thrombosis and infarction
• multiple gestations
• placental genetic mosaicism

maternal factors

• preeclampsia
• chronic hypertension
• maternal use of drugs, narcotics, alnohol and nicotine
• maternal malnutrition